Repetitive exposure to low-dose X-irradiation attenuates testicular apoptosis in type 2 diabetic rats, likely via Akt-mediated Nrf2 activation

Mol Cell Endocrinol. 2016 Feb 15:422:203-210. doi: 10.1016/j.mce.2015.12.012. Epub 2015 Dec 17.

Abstract

To determine whether repetitive exposure to low-dose radiation (LDR) attenuates type 2 diabetes (T2DM)-induced testicular apoptotic cell death in a T2DM rat model, we examined the effects of LDR exposure on diabetic and age-matched control rats. We found that testicular apoptosis and oxidative stress levels were significantly higher in T2DM rats than in control rats. In addition, glucose metabolism-related Akt and GSK-3β function was downregulated and Akt negative regulators PTP1B and TRB3 were upregulated in the T2DM group. Superoxide dismutase (SOD) activity and catalase content were also found to be decreased in T2DM rats. These effects were partially prevented or reversed by repetitive LDR exposure. Nrf2 and its downstream genes NQO1, SOD, and catalase were significantly upregulated by repetitive exposure to LDR, suggesting that the reduction of T2DM-induced testicular apoptosis due to repetitive LDR exposure likely involves enhancement of testicular Akt-mediated glucose metabolism and anti-oxidative defense mechanisms.

Keywords: Apoptosis; Nuclear factor erythroid 2-related factor 2; Oxidative stress; Testis; Type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Catalase / genetics
  • Catalase / metabolism
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Gene Expression Regulation / radiation effects
  • Male
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / radiation effects
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Signal Transduction / radiation effects
  • Testis / cytology
  • Testis / radiation effects*
  • Whole-Body Irradiation / methods*

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Catalase
  • Proto-Oncogene Proteins c-akt